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Masenge, A.

Oberholzer, H.M.

Van Antwerp, Maryna

Van Rooy, M.

English

Oberholzer, Hester Magdalena

Van Rooy, Mia-Jeanne

UPSpace at the University of Pretoria

Adenosine diphosphate and thromboxane A2 platelet activation in type II diabetes mellitusVan Antwerp M1, Oberholzer HM2, Masenge A, Van Rooy M1 (1 Department of Physiology, 2 Department of Anatomy)Introduction• Type II Diabetes Mellitus has become a global health concernand is associated with the increased risk for thrombotic events, including myocardial infarction and stroke.1• Platelets play an important role in the development of a blood clot through activation, aggregation and the formation of a fibrin network.• Adenosine diphosphate (ADP) and thromboxane A2 (TXA2) are two potent platelet activators and were found to be up regulated in diabetic patients, but platelet activation through these agonists has not been well defined.2The aim of this study was to elucidate whether diabetic platelets are more reactive towards ADP or TXA2, compared to healthy platelets and whether platelets in diabetic populations are primed for activation by these agonists by expressing more receptors.Methods:Flow Cytometry, Confocal Microscopy: Analyse receptor expression for ADP (P2Y1 and P2Y12) and TXA2 (TP) on platelet surfaces after stimulation (thrombin and collagen) or no stimulation .TEG Platelet Mapping: Test platelet activation in response to ADP and TXA2.Figure 1: Flow cytometry results of percentage positivity for P2Y1, P2Y12 and TPA-C: Unstimulated; D-F: Stimulated. Data expressed as median and IQR. P< 0.05• Flow cytometry data (n=10): no significant difference between control and diabetic platelet receptor expression in stimulated or unstimulated samples. • TEG data (n=8): significant difference in maximal (MA) amplitude (mm) of the clot between groups for kaolin treated samples, fibrin and ADP.Discussion and conclusion:• TEG data shows diabetic patients might have a risk for bigger thrombi (MA Kaolin ), greater fibrin formation (MA Fibrin ) and increasedsensitivity to ADP (MA ADP).• Preliminary data shows diabetic platelets do not express more receptors for P2Y1, P2Y12 and TP thus, greater ADP sensitivity might indicate increased signalling through these receptors.  References: 1. Pretorius L, Thomson GJA, Adams RCM, Nell TA, Laubscher WA, Pretorius E. Platelet activity and hypercoagulation in type 2 diabetes. Cardiovasc Diabetol. 2018 Nov 2;17(1):141.    2. Offermanns S. Activation of platelet function through G protein-coupled receptors. Circ Res. 2006 Dec 8;99(12):1293–304. Abbreviations: MA, Maximal amplitude; ADP, Adenosine diphosphate; AA, Arachidonic acid; Agg, aggregation.Values expressed as mean and SD. P< 0.05Results

Adenosine diphosphate and thromboxane A2 platelet activation in type II diabetes mellitus

https://repository.up.ac.za/bitstream/2263/87497/1/Van%20Antwerp_Adenosine_2021.pdf

Adenosine diphosphate and thromboxane A2 platelet activation in type II diabetes mellitus

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